Dehydroepiandrosterone (DHEA) having the formula: ##STR2##
and its sulfate ester (DHEAS) are secretory products of the human adrenal cortex. Both DHEA and DHEAS circulate in the blood stream at levels that vary with age in adult men and women. For example, blood plasma levels of DHEAS have been show to decrease fairly rapidly from a high level in newborns, then peak again in early advancing age (see, Orentreich, et al., J. Clin. Endocrinol. Metab., 59(3), 551 (1984).
DHEA has been used to treat a variety of ailments. U.S. Pat. No. 4,628,052 to Peat teaches the use of DHEA and other steroids for treating arthritis and non-specific joint pain. International Publication WO 93/21771 to Daynes, et al. teaches the use of DHEA to reduce abnormally elevated interleukin 6 levels to treat individuals with rheumatoid arthritis, bacterial meningitis, alcoholic liver cirrhosis, AIDS, and other pathologic conditions, as well as to treat burn victims and surgery patients.
DHEA has also been used to alleviate skin ailments. U.S. Pat. No. 4,496,556 to Orentreich teaches the use of DHEA and fatty acid esters thereof, including DHEA acetate, DHEA valerate and DHEA enanthate to treat dry skin. Japanese Patent Application 60-161912 to Ogawa et al., teaches cosmetic compositions containing a water-soluble DHEA salt to treat chapped skin. German patent No. DE 2147309 teaches the use of DHEA to treat psoriasis.
Non-steroid molecules, such as hydroxybenzoic acids and .alpha.-hydroxycarboxylic acids have also been used to treat skin conditions. .alpha.-Hydroxycarboxylic acids have been used to treat ichthyosis, hyperkeratoses, dandruff and acne (see, U.S. Pat. Nos. 3,879,537 to Van Scott et al.; 3,920,835, 3,988,470, and 4,234,599 to Van Scott et al.; 3,984,566 to Van Scott et al.; and 4,105,782 to Yu et al.; respectively). .alpha.-Hydroxycarboxylic acids have also been used to treat dry skin (see, U.S. Pat. Nos. 4,105,783 to Yu et al.; 4,194,007 to Van Scott et al.; 4,197,316 to Yu et al.; 4,380,549 to Van Scott et al.; 4,363,815 to Yu et al. and 4,091,171 to Yu et al. .alpha.-Hydroxycarboxylic acids have also been used to enhance the antiinflammatory action of corticosteroids (see, U.S. Pat. No. 4,246,261 to Van Scott et al.). U.S. Pat. No. 5,254,343 to Parah et el. discloses the use of salts of .alpha.-hydroxyacids in conjunction with steroids to minimize cutaneous atrophy, a side-effect of steroid application to the skin.
One of the drawbacks of using .alpha.-hydroxyacids for treating skin ailments of a patient is that at high concentrations, .alpha.-hydroxyacids are known to remove the outer layer of skin by effectively burning the skin off the patient. Such treatments are known in the art as "chemical peels." However, when improperly monitored, chemical peeling of the outer layer of skin using .alpha.-hydroxyacids can lead to inflammation, infection and scarring. Thus there is a need for a composition capable of providing the skin-healing benefits of .alpha.-hydroxyacids while avoiding the drawbacks such as those described above.
Salicylic acid has also been used to treat conditions of the skin. International Publication No. WO 93/10756, published Jun. 10, 1993 to Blank teaches the use of salicylic acid to regulate wrinkles and/or atrophy in mammalian skin. U.S. Pat. No. 5,262,407 to Leveque et al. teaches the use of C.sub.1 -C.sub.18 alkanoyl 5-acylsalicylic acids to treat aging skin.
One of the drawbacks associated with the use of DHEA in the treatment of skin is that the increased sebum production resulting from such treatment is accompanied by or associated with the formation of acne-like skin lesions in people who have a genetic tendency for acne. U.S. Pat. No. 4,542,129 to Orentreich teaches the use of a mixture of DHEA and a keratolytic agent, such as a hydroxybenzoic acid or an .alpha.-hydroxycarboxylic acid, to treat dry skin while deterring acne formation.
Thus, there is a need for a composition with skin healing properties of DHEA but that does not have the DHEA disadvantages. Similarly, there is a need for compounds having the advantageous properties of .alpha.-hydroxycarboxylic acids that can function more effectively with steroid compounds and without the deleterious effects of conventional .alpha.-hydroxyacids.
Moreover, when compositions comprising more than one agent useful for treating skin are intended to be formulated, solvents or vehicles which successfully dissolve or suspend one of the necessary agents may be completely ineffective in dissolving or suspending the other(s), and vice versa. This can result in an excessive amount of time, energy and manpower required for determining the proper formulation solvents or vehicles. Thus, there remains a need for such a composition which can be more efficiently formulated.
It is an object of the present invention to provide novel compounds with enhanced skin-healing properties. It is a further object to provide compounds which have the advantages of DHEA and keratolytic agents without the above-mentioned biological disadvantages or formulation problems.